MDI-301 is a synthetic retinoid. MDI-301, like RA, induces collagen synthesis and reduces expression of collagen-degrading matrix metalloproteinases in the skin. This agent also induces epidermal thickening. However, unlike RA, MDI-301 is non-irritating when applied topically. In a recent study we showed that MDI-301 was effective in promoting the healing of superficial abrasion wounds in hairless rats with skin made atrophic by corticosteroid treatment. Given these findings, we propose in this Phase I SBIR grant application to topically treat aged hairless rats with MDI-301 for a two-week period. Control animals will be treated with vehicle alone or with RA as a positive control. During the treatment period, animals will be examined for skin irritation. Following treatment, skin will be obtained and analyzed for collagen production and for elaboration of collagen-degrading enzymes. In other animals, superficial abrasion wounds will be induced following treatment. Healing in control and MDI-301-treated animals will be compared. If we can demonstrate that MDI-301 promotes healing of superficial abrasion wounds in aged skin but does not induce significant irritation, this will provide a strong impetus for development of this agent as a non-irritating "wound preventative". The medical benefit and commercial potential will be significant. PUBLIC HEALTH RELEVANCEThe goal of this work is to develop a non-irritating retinoid for topical use in aged skin. The non-irritating retinoid will, hopefully, improve the structure and function of aged skin so that it will resist formation on non-healing wounds. It should do so without irritation. [unreadable] [unreadable] [unreadable]